Dottorato in TECNOLOGIE INNOVATIVE NELLE MALATTIE DELLO SCHELETRO,
DELLA CUTE E DEL DISTRETTO ORO-CRANIO-FACCIALE

Titolo della tesi: Diagnostic performance of multiparametric ultrasound in comparison with CT-angiography, MR-angiography and histology in the quantitative and qualitative evaluation of the carotid plaque.

◦ Introduction Nowadays the decision making in the management of carotid atherosclerotic pathology is essentially related to the grade of stenosis along with the clinical condition of the patients. However there are several evidences about the importance of the qualitative evaluation of the atheromatous plaque to differentiate stable from vulnerable ones, which are prone to the rupture. In this field color-Doppler ultrasound (CDUS) is the first line imaging modality. In the last decades several new tools and technologies have been developed and it is currently possible to assess the morphologic features of the plaque with a multiparametric ultrasound examination (MPUS), composed of CDUS, contrast-enhanced ultrasound (CEUS) and 3D ultrasound (3DUS). ◦ Aim of the Study To evaluate the diagnostic accuracy of MPUS (CDUS, CEUS and 3DUS with 3D Arterial Analysis software) in the assessment of the grade of stenosis and of the vulnerability features of the plaque in comparison with CT-angiography (CTA), MR-angiography (MRA) and histology. ◦ Materials and Methods Forty-four patients scheduled to undergo endarterectomy were recruited on the basis of the following criteria: asymptomatic patients with stenosis>60% or symptomatic patients with stenosis >50%. All of them underwent MPUS, CTA (which was the imaging gold standard for the definition of the grade of stenosis) and MRA. After endarterectomy the surgical specimens were examined at histology, which was the gold standard for the assessment of the vulnerability features. Sensitivity, specificity, positive predictive value (PPV>), negative predictive value (NPV) and the area under the curve (AUC) were calculated for each of the ultrasound methods and for CTA and MRA. The concordance among the different techniques was evaluated with Cohen’s kappa. ◦ Results CTA: 40 plaques were found and considered high grade of stenosis; 31 plaques were identified as vulnerable and 30 of these were confirmed at histology, while 8 of the remaining plaques were correctly classified as stable, while 5 false negative cases. These results yielded a sensitivity of 85.7%, a specificity of 88.9%, a PPV of 96.8% and a NPV of 61.5%. The AUC was 87.3%. Histologic Examination: 35 of the 44 plaques sent to histology after endarterectomy were classified as vulnerable: 15 of these because of a lipid core; 10 because of the presence of inflammatory infiltrate; 10 because of significant presence of neovascularization. MRA: 36 out of the 40 plaques classified as high grade of stenosis at CTA were confirmed at MRA, with a sensitivity of 90.0%, a specificity of 100%, a PPV of 100%, a NPV of 50% and an AUC of 95%. Thirty-one out of the 35 plaques classified as vulnerable at histology were correctly defined at MRA with a sensitivity of 88.6 %, a specificity of 88.9%, a PPV of 96.9%, a NPV of 66.7% and a total AUC of 88.7%. CDUS: 34 out of the 40 plaques with high grade of stenosis were identified at CDUS, with a sensitivity of 85.0%, a specificity of 75%, a PPV of 97.1%, a NPV of 33.3% and an AUC of 80.0%. Twenty-eight out of the 35 vulnerable plaques confirmed by histology were detected with a sensitivity of 80.0%, a specificity of 66.7%, a PPV of 90.3%, a NPV of 46.2% and a total AUC of 73.3%. 3D Arterial Analysis Software: 39 out of the 40 plaques with high grade of stenosis were identified with a sensitivity of 97.5%, a specificity of 50%, a PPV of 95.1%, a NPV of 66.7% and a AUC of 73.8% were reached. Thirty-four out of the 35 histologically proven vulnerable plaques were correctly classified by 3DAA with a sensitivity of 97,1%, a specificity of 44.4%, a PPV of 87.2%, a NPV of 80.0% with a total AUC of 70.8%. CEUS: 37 out of the 40 high-grade stenosis plaques detected by CTA were identified, with a sensitivity of 92.5%, a specificity of 100%, a PPV of 100%, a NPV of 57.1% and a AUC of 96.3%. Thirty-two out of the 35 vulnerable plaques confirmed by histology were correctly classified, with a sensitivity of 91.4%, a specificity of 88.9%, a PPV of 97.0%, a NPV of 72.7% with a total AUC of 90.2%. No adverse effects related to the diagnostic methods were reported. ◦ Conclusions In conclusion, the addition of 3DAA and CEUS to the routine ultrasound examination allows a more accurate measurement of the grade of stenosis and characterization of the plaque vulnerability in comparison with CDUS alone, yielding results which are comparable with those of CTA.